High Non-Relapse Mortality Remains Barrier to Allogeneic Transplantation Success Rates for Patients With Myelofibrosis
Key Clinical Summary
- Population and Design: Retrospective study of 42 patients (median age 64 y) with primary (52%) or secondary MF (48%) undergoing allogeneic HCT, most with high comorbidity (HCT-CI ≥ 3, 86%); pre-transplant JAK inhibition used in 71%, and PTCy for GVHD prophylaxis in a subset; median follow-up 107 months.
- Efficacy: 1-year OS 67%, NRM 31%; at 5 years, OS 51%, DFS 46%, NRM 36%, relapse 17%. Favorable cytogenetics predicted improved OS (HR 0.31; P=0.005), DFS (HR 0.36; P = 0.012), and lower relapse risk (HR 0.25; P=0.035). Matched donors (MRD/MUD) were associated with less relapse versus haploidentical donors (HR 0.26; P = 0.043).
- Clinical Relevance: Despite advances in transplant and JAK inhibitor use, non-relapse mortality remains high, limiting long-term benefit. Favorable cytogenetics and donor matching are key prognostic factors, and earlier transplantation, refined conditioning, and optimized JAK inhibitor strategies may improve outcomes in MF post-allo-HCT.
Allogeneic stem cell transplantation (allo-HCT) success for patients with primary or secondary myelofibrosis (MF) who received Janus kinase inhibitor therapy, and long-term survival remains limited by high non-relapse mortality (NRM), according to study results published in Blood.
For patients with primary or secondary MF, allo-HCT remains the only curative option. However, outcomes remain suboptimal for patients with certain disease-specific characteristics. Researchers conducted a retrospective study to determine the impact of JAK inhibition pre-transplant and post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis on patient outcomes.
Overall, 42 patients with primary or secondary MF were included, the median patient age was 64 years (range 39 to 75), and 86% had a HCT-comorbidity index (HCT-CI) of ≥3. Most patients had primary MF (52%), JAK2 mutations (62%), and unfavorable cytogenetics (33%). Donor types included matched related (MRD, 21%), matched unrelated (MUD, 36%), haploidentical (HAPLO, 40%), and cord blood (2%), with reduced-intensity conditioning (RIC) used in 74%. Pre-transplant JAK inhibition was administered in 71% of patients, and post-transplant cyclophosphamide (PTCy) was used for GVHD prophylaxis in a subset.
At a median follow-up of 107 months, 7% of patients experienced graft rejection. Grade 2 to 4 acute GVHD incidence was 20 days and grade 3 to 4 incidence was 43 days. The 1-year overall survival (OS) was 67% and the NRM was 31%. Additionally, the 5-year OS was 51%, disease-free survival (DFS) was 46%, NRM was 36%, and relapse incidence was 17%. Patients who underwent transplant between 2017 to 2024 had a 5-year NRM of 38.9%, compared with patients who underwent transplant between 2011 and 2016 (33.3%).
In multivariable analysis, favorable cytogenetics was significantly associated with improved OS (hazard ratio [HR], 0.31; P = 0.005), DFS (HR, 0.36; P = 0.012), and reduced relapse risk (HR, 0.25; P = 0.035).
Use of MRD/MUD donors also reduced relapse compared to HAPLO donors (HR, 0.26; P = 0.043). Other variables, including age, comorbidity index, conditioning intensity, JAK inhibitor use, and PTCy, were not predictive of transplant outcomes.
The researchers concluded, “high NRM remains a significant barrier to transplant success in MF despite more frequent use of pre-transplant JAK inhibition and improvements in transplant techniques that have resulted in better outcomes in other hematologic malignancies.”
They added, “Additional strategies, such as earlier transplantation, improved patient selection, pre-transplant management of splenomegaly, choice of conditioning regimens, and optimizing pre- and post-transplant use of JAK inhibition, are likely required to improve post-transplant survival.”
Source:
Solomon S, Maakaron J, Bachier-Rodriguez L, et al. Outcomes for allogeneic transplant in myelofibrosis remain suboptimal in the modern era despite increased use of post-transplant cyclophosphamide and pre-transplant JAK inhibition. Blood. November 3, 2025. doi:10.1182/blood-2025-7830
